The calcium binding protein calmodulin regulates many enzymatic processes in the brain including those that synthesize and release neurotransmitters. 1. It is proposed to study this molecule at the level of the gene in order to elucidate tht structure of the calmodulin gene in the mammalian organism. The nucleotide sequences in the protein coding region, the intron-exon junctions, and possibly in the flanking region of the gene will be determined. cDNA probes derived from a brain lambda gt 11 cDNA library will be used to screen for calmodulin clones contained in a rat genomic library. The structure and organization of the rat calmodulin gene will be determined by restriction mapping and by sequencing the DNA. 2. In collaboration with Dr. Detera-Wadleigh at the Clinical Neurogenetics Branch, MHIRP, NIMH, the isolated DNA will be used as a probe to screen for restriction fragment length polymorphisms at the calmodulin locus to determine whether such polymorphisms correlate with affective disorders and schizophrenia. Human genomic DNA is isolated from lymphoblasts. Screening is accomplished by Southern blot analysis. 3. In the hippocampal neurons of aged rats the calcium dependent after-hyperpolarizations are prolonged. Calmodulin levels in the brain decrease with age. It is not known whether calmodulin gene expression in one area of the brain is influenced by developmental and aging processes to the same extent as in other brain structures. The expression of the calmodulin gene in different parts of the rat brain at various stages of development and senescence will be investigated. Here the techique of "Northern" blotting is employed.